Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation

Primary Objective:

• Determine the proportion of patients with full donor T-cell chimerism at Day 28 following
hematopoietic cell transplantation.

Secondary Objectives:

- Determine the risk of disease progression, overall and event free survival, and
non-relapse mortality, following treatment with TLI; ATG; and TBI.

- Determine the incidence of acute and chronic GVHD following treatment with TLI; ATG; and
TBI.

Exploratory Objectives:

• Determine the changes in frequency of hematopoietic stem, progenitor, and mature cell
subsets and the changes in cytokine milieu and cellular architecture in the bone marrow of
patients receiving TLI compared to TLI+TBI.

INCLUSION CRITERIA

- Has a human leukocyte antigen (HLA)-matched or single allele mismatched adult sibling
donor or unrelated donor.

- Acute myeloid leukemia (AML); myelodysplastic syndrome (MDS); myeloproliferative
disease syndrome (MPD)]; chronic lymphocytic leukemia (CLL); B- or T-cell non Hodgkin
lymphoma (NHL); Hodgkin lymphoma (HL); or chronic myelomonocytic leukemia (CMML),
suitable for treatment with allogeneic transplant after TLI and ATG reduced intensity
conditioning.

- Considered at high-risk for regimen-related toxicity from fully-ablative transplant
conditioning (therefore reduced-intensity conditioning is recommended).

- Ability to understand and the willingness to sign a written informed consent document.
Patients must have signed informed consent to participate in the trial.

EXCLUSION CRITERIA

- Uncontrolled bacterial, viral or fungal infection defined as currently taking
medication and progression of clinical symptoms.

- Progressive hemato lymphoid malignancy despite conventional therapy.

- Chronic myelogenous leukemia (CML).

- Active CNS involvement of the underlying malignancy.

- HIV positive

- Pregnant or lactating

- Prior malignancy (EXCEPTION: diagnosed > 5 years ago without evidence of disease, OR
treated ≤ 5 years ago but have a greater than 50% chance of life expectancy of ≥ 5
years for that malignancy).

- Have a psychiatric disorder(s) or psychosocial circumstance(s) which in the opinion of
the primary physician would place the patient at an unacceptable risk from transplant.

- Left ventricular ejection fraction (LEVF) < 30%, or uncontrolled cardiac failure

- Diffusing capacity of lung for carbon monoxide (DLCO) < 40% predicted

- Total bilirubin > 3 mg/dL

- Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase
(SGPT) > 4 x upper limit of normal (ULN)

- Creatinine > 2 mg/dL and an estimated creatinine clearance < 40 mL/min

- Poorly-controlled hypertension despite multiple antihypertensive medications

- Karnofsky Performance Status (KPS) < 60%